Podcast
Questions and Answers
Which enzyme is involved in the reduction of aldehydes to alcohols during metabolic pathways?
Which enzyme is involved in the reduction of aldehydes to alcohols during metabolic pathways?
What is the primary function of Alcohol dehydrogenase (ADH) in Phase I metabolic reactions?
What is the primary function of Alcohol dehydrogenase (ADH) in Phase I metabolic reactions?
Which functional groups are least likely to undergo reduction in Phase I metabolic pathways?
Which functional groups are least likely to undergo reduction in Phase I metabolic pathways?
What type of metabolic pathway is represented by the conversion of alcohols into their corresponding aldehydes?
What type of metabolic pathway is represented by the conversion of alcohols into their corresponding aldehydes?
Signup and view all the answers
Which pathway involves the removal of functional groups from a compound, specifically through transformations like desulfuration?
Which pathway involves the removal of functional groups from a compound, specifically through transformations like desulfuration?
Signup and view all the answers
Phase I metabolic reactions generally involve which of the following processes?
Phase I metabolic reactions generally involve which of the following processes?
Signup and view all the answers
What is the function of Aldehyde dehydrogenase (ALDH) in the context of metabolic pathways?
What is the function of Aldehyde dehydrogenase (ALDH) in the context of metabolic pathways?
Signup and view all the answers
The reduction of azo compounds in metabolic pathways is primarily catalyzed by which enzyme?
The reduction of azo compounds in metabolic pathways is primarily catalyzed by which enzyme?
Signup and view all the answers
In the context of metabolic pathways, what is the primary outcome of a reduction reaction involving an aldehyde?
In the context of metabolic pathways, what is the primary outcome of a reduction reaction involving an aldehyde?
Signup and view all the answers
What enzyme is primarily responsible for the reduction of azo compounds in metabolic pathways?
What enzyme is primarily responsible for the reduction of azo compounds in metabolic pathways?
Signup and view all the answers
Which of the following reactions is considered an example of oxidative dehalogenation?
Which of the following reactions is considered an example of oxidative dehalogenation?
Signup and view all the answers
What is likely the major metabolic pathway for converting duloxetine during its phase I reaction?
What is likely the major metabolic pathway for converting duloxetine during its phase I reaction?
Signup and view all the answers
What type of bond is primarily involved in carbon-oxygen bond oxidation reactions?
What type of bond is primarily involved in carbon-oxygen bond oxidation reactions?
Signup and view all the answers
Which of the following represents a characteristic of sulfur dealkylation?
Which of the following represents a characteristic of sulfur dealkylation?
Signup and view all the answers
In terms of metabolic pathways, what does the process of desulfuration primarily involve?
In terms of metabolic pathways, what does the process of desulfuration primarily involve?
Signup and view all the answers
Which metabolic process is essential in the detoxification of reactive sulfur species?
Which metabolic process is essential in the detoxification of reactive sulfur species?
Signup and view all the answers
What is the primary function of Phase I metabolism in drug metabolism?
What is the primary function of Phase I metabolism in drug metabolism?
Signup and view all the answers
Which of the following reactions is NOT typically categorized under Phase I metabolic pathways?
Which of the following reactions is NOT typically categorized under Phase I metabolic pathways?
Signup and view all the answers
Which enzyme is primarily responsible for catalyzing Phase I oxidation reactions?
Which enzyme is primarily responsible for catalyzing Phase I oxidation reactions?
Signup and view all the answers
During oxidative dehalogenation in Phase I metabolism, what is typically removed from the drug molecule?
During oxidative dehalogenation in Phase I metabolism, what is typically removed from the drug molecule?
Signup and view all the answers
What is the result of Phase I N-dealkylation in drug metabolism?
What is the result of Phase I N-dealkylation in drug metabolism?
Signup and view all the answers
Which of the following functional groups may be introduced or unmasked during Phase I metabolic reactions?
Which of the following functional groups may be introduced or unmasked during Phase I metabolic reactions?
Signup and view all the answers
What is the role of reduction in Phase I metabolism?
What is the role of reduction in Phase I metabolism?
Signup and view all the answers
Which metabolic pathway is characterized by multiple sequential reactions often requiring competing pathways?
Which metabolic pathway is characterized by multiple sequential reactions often requiring competing pathways?
Signup and view all the answers
Study Notes
Principles of Drug Action: Chemical Basis of Drug Metabolism I
- Lecture 24 covers the chemical basis of drug metabolism.
- Medicinal chemistry focuses on drug-target interactions, drug discovery, development, and optimization.
- Physicochemical properties of drugs include functional groups (FG), acidity/basicity, salt and solubility, and chirality.
- Drug targets include enzymes and receptors.
- Drug metabolism is crucial for terminating drug activity, determining the duration and intensity of the pharmacological response, and converting prodrugs to active drugs.
- Drug metabolism primarily occurs in the liver, but also in other organs (GI, kidney, lung, skin, CNS, placenta, fetus).
- Microsomes, cytosol, and mitochondria are involved in drug metabolism.
- The first-pass effect describes the metabolism of orally absorbed drugs in the liver before systemic distribution.
Drug Metabolism Phases
- Drug metabolism occurs in two main phases: Phase I and Phase II.
- Phase I reactions (oxidation, reduction, hydrolysis) add polar handles to the molecule (e.g. OH, -NH2, -COOH).
- Cytochrome P450 (CYP450) enzymes are crucial for Phase I oxidation reactions.
- Phase II reactions involve conjugation (adding endogenous compounds) to the drug molecules.
- Phase I reactions often prepare molecules for Phase II reactions.
Pharmacokinetics: ADME
- Pharmacokinetics describes how the body handles drugs.
- Absorption, Distribution, Metabolism, and Excretion (ADME) are key concepts of pharmacokinetics.
- Absorption (how drugs enter the body) and Distribution (where drugs go in the body) are key processes.
- Metabolism (how drugs are broken down) and Excretion (how drugs leave the body) are essential processes following distribution.
- The liver plays a key role in drug metabolism.
Drug Distribution
- Drug distribution happens rapidly from blood vessels to tissues and organs through leaky blood vessels.
- Drugs cross blood vessel walls quickly through gaps between cells.
- Drug distribution fills the entire blood supply within 1 minute of absorption..
- Uneven distribution around the body based on blood supply.
- Distribution, binding to macromolecules, storage in fat tissue (e.g. barbiturates) or bone cause Blood concentration to drop rapidly after absorption..
CYP450
- CYP450 enzymes catalyze oxidation and reduction reactions.
- CYP450 contains a heme molecule bound to an iron atom.
- CYP450's role in drug metabolism involves inserting oxygen atoms into drug molecules and is key to the process.
- Different CYP450 isoforms exist, influencing patient variability in drug metabolism and potential side-effects.
- The mechanism of CYP450 enzymatic oxidation involves the addition of oxygen molecules and the addition of hydrogens based on the steps (reduction).
Drug-Drug & Drug-Food Interactions
- Drugs impacting CYP450 activity can affect the metabolism of other drugs, resulting in variations in needed dosages.
- Foods like grapefruit juice may inhibit CYP450 activity, altering drug metabolism and dosages..
- Certain food and drug interactions exist.
Metabolic Pathways: Phase I Reactions
- Phase I metabolism converts chemicals to more polar metabolites by introducing or unmasking polar functional groups.
- This phase includes oxidation, reduction, and hydrolysis.
- Oxidation reactions add oxygen to or remove hydrogen from molecules, increasing their polarity. Reduction reactions add hydrogen atoms.. Hydrolysis reactions break bonds and add water molecules to metabolites.
Metabolic Pathways: Phase II Reactions
- Phase II reactions involve conjugation.
- Endogenous compounds bind to metabolites to further increase their polarity.
- This phase makes the metabolites more readily excreted from the body.
Drug Metabolism: Oxidation of Specific Functional Groups
- Aromatic rings, alkenes, aliphatic/ alicyclic carbon atoms, benzylic/ allylic carbon atoms, imine/carbonyl bonds, and amine, amide, and aromatic nitrogen atoms can undergo oxidation reactions by CYP450 enzymes..
Drug Metabolism: Reduction Reactions
- Reduction reactions involve adding hydrogen to or removing oxygen from metabolized substances by enzymes acting as biocatalysts.
Drug Metabolism: Hydrolysis
- Hydrolysis involves the addition of a water molecule to break a bond, typically occurs with esters, amides, and cyclic analogs.
Prodrugs
- Prodrugs are inactive compounds that are metabolized into active forms in the body.
- Prodrugs are often used to improve membrane permeability, lower the water solubility of foul-tasting drugs, mask toxicity/side effects, and enhance water solubility for intravenous administration.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
This quiz explores the chemical basis of drug metabolism as presented in Lecture 24. It delves into drug-target interactions, the phases of drug metabolism, and the significance of physicochemical properties in medicinal chemistry. Gain insights into the importance of drug metabolism in pharmacology and therapeutic responses.
